Diastolic Interventricular Septal Thickness Research Articles

Usefulness of quantitative 99mTc-pyrophosphate SPECT/CT for predicting the prognosis of patients with wild-type transthyretin cardiac amyloidosis

PurposeWild-type transthyretin-related amyloidosis cardiomyopathy (ATTRwt-CM) is an increasingly recognized cause of heart failure especially in elderly patients. The purpose of the present study was to determine retrospectively whether the quantitative indices of 99mTc-pyrophosphate (PYP) SPECT/CT help to predict the prognosis of ATTRwt-CM patients when compared with other clinical parameters.Materials and methodsSixty-eight patients with biopsy-proven ATTRwt-CM who underwent PYP SPECT/CT were enrolled. Baseline clinical characteristics, echocardiographic parameters, and qualitative and/or quantitative indices of planar and SPECT/CT imaging in PYP scintigraphy for each patient were included. For quantitative analysis of SPECT/CT, the accumulation ratio of PYP in the septum, posterior, anterior, lateral, and apex walls to the cavity pool was calculated as the septal wall-to-cavity ratio (Se/C), lateral wall-to-cavity ratio (La/C), anterior wall-to-cavity ratio (An/C), inferior wall-to-cavity ratio (In/C), and apical wall-to-cavity ratio (Ap/C), respectively. Endpoints for prognostic accuracy evaluation were cardiac death or hospitalization due to heart failure. Event-free survival rate was evaluated through Cox proportional hazards regression analysis, providing estimated hazard ratios (HRs) with 95% confidence intervals (CIs) and Kaplan–Meier curves.ResultsHigh-sensitivity cardiac troponin T (hs-cTnT), La/C, age, interventricular septal thickness in diastole, and E/e′ ratio in the septal wall were significantly associated with event-free survival (P < 0.05). For a multivariable Cox proportional hazards analysis, hs-cTnT (HR 1.153; 95% CI 1.034–1.286; P < 0.01), La/C (HR 2.091; 95% CI 1.012–4.322; P = 0.046), and age (HR 1.116; 95% CI 1.007–1.238; P = 0.037) were significant independent prognostic factors.ConclusionThis study indicated that the quantitative indices of PYP SPECT/CT can help to predict the prognosis of ATTRwt-CM patients.

Secretion of Atrial Natriuretic Peptide (Anp), Heart Reconditioning and Remolding in Elite Endurance Trained Athletes

Aim / Objective: The aim of this study was to evaluate the effect of maximal exercise on the level of cardiac remolding and Atrial Natriuretic Peptide (ANP) in elite athletes as compared to sedentary healthy subjects and correlation of ANP with the adaptation of athlete’s heart and cardiac remodeling (if any) Place and Duration of Study: The present study was carried out at the Department of Physiology, Army Medical College, with collaboration of Armed Forces Institute of Cardiology (AFIC) Rawalpindi from June 2003 to May 2004. Methodology: A total number of 44 subjects were included in this study. These comprised of 22 elite endurance athletes and 22 healthy sedentary volunteers as controls. All subjects were examined clinically to rule out the cardiovascular and pulmonary diseases on the basis of medical history, physical examination, and echocardiography. All the selected subjects were examined on a Toshiba Power Vision 6000 echocardiograph for assessing and measuring their LV end-diastolic internal diameter (LVIDd), Diastolic interventricular septal thickness (IVSTd), diastolic posterior wall thickness (PWTd). The left ventricular mass was (LVM) was calculated by using the Devereux formula. They were subject to go for ergometer cycle exercise before breakfast. The Blood samples were drawn before and after exercise to assess the level of ANP in their samples. Results: It was found that LVIDd, IVSTd, PWTd, LVM were higher in athletes as compared to their age, sex and BMI matched controls. The ANP levels in athlete’s plasma were also high in post and pre exercise sample as compared to controls. Conclusion: Systolic blood pressure, Diastolic Blood Pressure and heart rate are lower in endurance elite athletes than matched sedentary controls. The maximal Exercise increases the level of Atrial Natriuretic Peptide (ANP) in elite athletes significantly as compared to sedentary healthy controls. There was a Positive correlations between ANP and LVIDd, IVSTd, PWTd, and LVM while there was negative correlation between ANP and heart rate, ANP and Blood pressure. However, none of correlation was found to be statistically significant. Keywords: Athlete’s Heart, ANP, Cardiac remodeling in athletes, Echocardiography of heart

Low serum 25-Hydroxy (OH) vitamin D levels are associated with increased arterial stiffness in healthy children: An echocardiographic study from Turkey.

Arterial stiffness refers to arterial wall rigidity, particularly in central vessels, and is an independent predictor of cardiovascular disease in many chronic diseases. 25-Hydroxy (OH) vitamin D has beneficial effects on blood pressure, vascular endothelial function, and arterial stiffness; most importantly, its deficiency is common worldwide. Therefore, we aimed to elucidate the role of 25-OH vitamin D deficiency in arterial stiffness development and its relationship with arterial stiffness in healthy children. This study included 80 patients with low levels of 25-OH vitamin D and 40 healthy control subjects. The study participants were then divided into three groups: group 1 consisted of patients with a deficient 25-OH D level of<19.9ng/ml, group 2 with an insufficient 25-OH D level between 20 and 29.9ng/ml; group 3 were considered control group with a sufficient serum 25-OH vitamin D level of ≥30ng/ml. Aortic strain, distensibility, stiffness index, and standard left ventricular measurements were calculated using M-mode echocardiographic data. Left ventricular mass index (LVMI) and inter-ventricular septal diastolic thickness (IVST) appeared to increase in group 1 compared to groups 2 and 3. Aortic strain and distensibility were significantly decreased in group 1, whereas aortic stiffness index and elastic modulus were significantly increased. The aortic stiffness index was negatively correlated with serum 25-OH vitamin D levels; however, aortic strain, aortic distensibility, and LVMI were positively correlated. Our study results revealed a significant relationship between 25-OH vitamin D levels indicative of a deficiency and aortic stiffness. Hence, we suggest that arterial stiffness may also occur in healthy children with a 25-OH vitamin D deficiency. Future in-depth studies are needed to understand the exact mechanisms underlying the aortic stiffness development associated with 25-OH vitamin D deficiency.

Sex-Disparity in the Association Between Birthweight and Cardiovascular Parameters in 4-Year-Old Children: A Chinese Cohort Study.

Background: Sex-related differences in cardiovascular parameters have been well documented in adults, and the impact of birthweight on cardiovascular health in later life has been acknowledged. However, data was limited regarding the association between birthweight and cardiovascular outcomes at an early age, and the sex-disparity in the association remained unclear.Objective: To investigate the association between birthweight and cardiovascular parameters in 4-year-old children. Furthermore, to explore whether sex-disparity exist in this association or in cardiovascular risk.Methods: Follow-up data from the Shanghai Birth Cohort (SBC) was analyzed. Detailed perinatal information including both maternal and offspring datum were recorded. Blood pressure, echocardiography, and anthropometry assessment were conducted during the follow-up of 4-year-old children. Linear regression models were used to analyze the association between birthweight and left ventricle (LV) structure and function changes in each sex and birthweight category. Multivariable logistic regression models were used to compare risk of left ventricular hypertrophy (LVH) in different birthweight subgroups.Results: Overall, macrosomia was significantly associated with thickened LV posterior wall thickness in systole [LVPWs, (β = 0.26, 95% CI: 0.06, 0.45)] and diastole [LVPWd, (β = 0.18, 95% CI: 0.06, 0.30)], and thickened interventricular septal thickness in diastole [IVSd, (β = 0.16, 95% CI: 0.05, 0.28)]. Boys with macrosomia showed a higher left ventricle mass index [LVMI, (β = 1.29, 95% CI: 0.14, 2.43)], thickened LVPWs (β = 0.30, 95% CI: 0.05, 0.56) and LVPWd (β = 0.21, 95% CI: 0.06, 0.36), and thickened IVSd (β = 0.23, 95% CI: 0.09, 0.36). However, no significant association of structural changes was found in girls. Furthermore, an increased risk of LVH was found solely in macrosomic boys (OR = 2.79, 95% CI: 1.17, 6.63).Conclusion: Children with macrosomia developed cardiovascular changes as early as 4 years of age. Macrosomia was associated with LV structural changes and higher LVH risk in pre-school-aged boys, while no association was found in girls.

THE RELATIONSHIP BETWEEN EPICARDIAL FAT TISSUE THICKNESS AND RISK OF FREQUENT PREMATURE VENTRICULAR CONTRACTIONS

Objectives: This study aimed to evaluate the relation between epicardial fat tissue (EFT) thickness and frequent premature ventricular contractions. Methodology: In this cross-sectional study, patients with no structural heart diseases diagnosed with PVCs on a 24 holter rhythm monitoring were included. EFT thickness was measured by 2-dimensional transthoracic echocardiography. PVCs of more than 10 per hour were considered as frequent PVCs. To investigate the effect of independent variables, univariate logistic regression was performed. Results: Of total 50 studied patients, 64% were females. The mean age of subjects was 46.8 ± 13.1 years. Twenty-five patients were experiencing frequent PVCs of &gt;10 per hour. In univariate analysis, age (OR= 1.05, 95 % CI; 1.01-1.10, p=0.050), left ventricular end diastolic diameter (LVEDD) (OR= 1.14, 95 % CI; 1.01-1.28, p=0.036) and left atrial (LA) diameter (OR= 1.35, 95 % CI; 1.11-1.62, p=0.002) were significantly associated with developing frequent PVC. EFT thickness was positively correlated with age (r= 0.389, p= 0.005) and inter-ventricular septum thickness in diastole (IVSD) (r= 0.384, p= 0.006). No significant correlation between EFT and PVCs was found (p=0.669). Conclusion: Patients with frequent PVCs had significantly higher LVEDD and LA diameter. Although patients with higher EFT thickness were more likely to experience frequent PVCs, there was no statistically significant correlation between EFT thickness and frequent PVCs.

Maternal Fructose Intake Exacerbates Cardiac Remodeling in Offspring with Ventricular Pressure Overload.

Recent studies demonstrated that metabolic syndrome and cardiovascular diseases could be elicited by developmental programming, which is regulated by prenatal nutritional and environmental stress. In this study, we utilized a rat model to examine the effect of excessive maternal fructose intake during pregnancy and lactation on cardiac development and progression of pressure overload-induced cardiac hypertrophy in offspring. Transverse aortic constriction (TAC) was performed on 3-month-old male offspring to induce ventricular pressure overload. Four weeks post-TAC, echocardiographic assessment as well as histopathological and biochemical examinations were performed on the myocardium of the offspring. Echocardiographic and gross examinations showed that heart weight, interventricular septal thickness in diastole (IVD; d), and left ventricular posterior wall thickness in diastole (LVPW; d) were elevated in offspring with TAC and further increased by maternal fructose exposure (MFE). However, the left ventricular ejection function was not significantly affected. Myocardial histopathological examination revealed that the indices of fibrosis and oxidative stress were higher in offspring with MFE and TAC than those in animals receiving either treatment. Molecular examinations on the myocardium demonstrated an MFE-induced upregulation of p38-MAPK signaling. Next generation sequence (NGS) analysis indicated a modulation of the expression levels of several cardiac hypertrophy-associated genes, including GPR22, Myh7, Nppa, P2RX4, and Npy by MFE. Subsequent RT-PCR indicated that MFE regulated the expression levels of genes responsive to cardiac hypertrophy (i.e., Myh-7, ANP) and oxidative stress (i.e., GR, GPx, and NQO-1). In conclusion, MFE during pregnancy and lactation modulated myocardial gene expression, increased oxidative stress, and exacerbated ventricular pressure overload-induced cardiac remodeling in rat offspring.

A Study of Echocardiographic Changes in Patients with Newly Diagnosed Primary Hypothyroidism: A Cross-sectional Study

Background: Hypothyroidism is known to cause reversible cardiac dysfunction in humans. Thyroid hormone alters the cardiovascular hemodynamics. This study was performed to assess echocardiographic changes in untreated newly diagnosed primary hypothyroid states as such studies are scarce in our setting.Methods: This hospital based cross-sectional study was conducted among 71 patients with newly diagnosed primary hypothyroidism who presented to the medicine outpatient department, at Universal College of Medical Sciences and Teaching Hospital (UCMS-TH), Bhairahawa, Nepal from December 2018 to June 2020 after taking ethical clearance from institutional review committee (UCMS/IRC/212/18). Thyroid function test and echocardiography were carried out in patients under study. The data was analyzed with SPSS Version 16.Results: A total of 71 patients (52 females and 19 males) with primary hypothyroidism were enrolled for the study. Among these 58 cases were overt/clinical hypothyroidism, and 13 cases were subclinical hypothyroidism. Echocardiography was abnormal in 63.4% of cases with 43.7% showing diastolic dysfunction, 18.3% diastolic interventricular septal thickness abnormality, 8.5% diastolic left ventricular posterior wall thickness abnormality, and 8.4% pericardial effusion. Conclusion: Our study found diastolic dysfunction, diastolic interventricular septal thickness abnormality, diastolic left ventricular posterior wall thickness abnormality, and pericardial effusion as the common echocardiographic change in patients with newly diagnosed primary hypothyroidism. Therefore, our study highlights the need for cardiac evaluation of patients with primary hypothyroidism so that early intervention can be performed to improve the clinical outcome.

Ultrasonography to detect cardiovascular damage in children with essential hypertension

BackgroundEssential hypertension in adults may begin in childhood. The damages to the heart and blood vessels in children with essential hypertension are hidden and difficult to detect. We noninvasively examined changes in cardiovascular structure and function in children with hypertension at early stage using ultrasonography.MethodsAll patients with essential hypertension admitted from March 2020 to May 2021 were classified into simple hypertension (group 1, n = 34) and hypertension co-existing with obesity (group 2, n = 11) isolation. Meanwhile 32 healthy children were detected as control heathly group (group 3). We used pulse-wave Doppler to measure carotid–femoral pulse wave velocity (cfPWV), intimal–medial thickness (cIMT) and distensibility of carotid artery (CD). Cardiac structure and function (left atrial diameter [LAD], left ventricular mass [LVM], LVM index [LVMI], relative wall thicknes [RWT], end-diastolic left ventricular internal diameter [LVIDd], diastolic interventricular septum thickness [IVSd], diastolic left ventricular posterior wall thickness [LVPWd], root diameter of aorta [AO], E peak, A peak, E' peak, A' peak, E/E' ratio, and E/A ratio) were measured by echocardiography.ResultsThe cfPWV of children in group 1 and group 2 were significantly higher than healthy children in group 3. Significant differences were observed in LVM, LVMI, RWT, LVIDd, IVSd, LVPWd, LAD, A peak, E' peak, A' peak, and E/E’ among three groups.ConclusionChildren and adolescents with essential hypertension demonstrate target organ damages in the heart and blood vessels.

Predictors and outcomes of acute kidney injury during autologous stem cell transplantation in AL amyloidosis.

Acute kidney injury (AKI) is a common complication after high-dose melphalan and autologous stem cell transplantation (HDM/SCT) in patients with light chain (AL) amyloidosis. However, its incidence, predictors and outcomes are not well known. This observational study included 223 patients with AL amyloidosis who underwent HDM/SCT. AKI was defined as an increase in serum creatinine to ≥1.5 times the baseline occurring within the first 30 days of HDM/SCT. The median age was 58 years (range: 30-77). Kidney and cardiac involvement were present in 86.1% and 56.8%, respectively. The median estimated glomerular filtration rate (eGFR) was 83.5 mL/min/1.73 m2 (range: 9-213) and proteinuria was 2899 mg/day (range: 0-19 966). AKI occurred in 29.1% of patients. Dialysis was initiated in 15 patients (6.7%) and of these 12 (80%) were able to discontinue dialysis. Most of the episodes of AKI occurred within the first 2 weeks; with a median follow-up of 4.5 years (range: 0.1-16.5), AKI was associated with increased overall mortality [hazard rato (HR) = 4.53, 95% confidence interval (CI) 2-10.23]. The 10-year overall survival was 87.1% without AKI, versus 56.9% with AKI. AKI was also associated with an increased risk for end-stage kidney disease (ESKD) (HR = 4.6, 95% CI 1.44-14.38). The risk of developing ESKD at 10 years was 18.9% with AKI, versus 8.1% without AKI. Several risk factors were found and using multivariate logistic regression, a prediction model was developed that included three readily available variables: eGFR <60 mL/min/1.73 m2, interventricular septal thickness in diastole >12 mm and albumin <3 g/dL. This model was able to predict AKI development with an area under the curve of 0.8. AKI is common in the post-HDM/SCT period and it leads to increased risk for ESKD and death. Our prediction model is an easily deployable tool in clinical settings as part of the discussion with patients who are being prepared for HDM/SCT.

Relationship of left ventricular and atrial dimensions with moderate to severe left ventricular diastolic dysfunction (grade II and above).

Left ventricular diastolic dysfunction (DD) is an entity in which the ventricle fails to fill up properly due to impaired ventricular relaxation and/or decreased compliance. The diagnosis of diastolic dysfunction is based on a variety of parameters in doppler echocardiograpy. However, some parameters like interventricular septal thickness in diastole (IVSd), posterior wall thickness in diastole (PWd), left ventricular internal end diastolic and systolic diameters (LVIDD and LVISD) along with left atrial diameters (LAD) have yet to be evaluated for the diagnostic workup of DD. A case control study was done in the cardiology department from patient records from 2016 to 2018. Patients were diagnosed as diastolic dysfunction grade II and above by doppler echocardiography. IVSd, PWd, LVIDD, LAD, LVISD were obtained through 2-D echocardiography. Patients with DD had greater LAD, IVSd and PWd and decreased LVIDD and LVISD as compared to control group. Overall, IVSD was the most significant predictor (OR 1.52 95%CI 1.35-1.71) of DD followed by PWd and LAD. Similarly, LAD, IVSd and PWd had higher sensitivity and specificity than LVIDD and LVIDS. IVSd, LAD and PWd showed significant performance in the diagnosis of diastolic dysfunction and hence can be used as a screening and diagnostic tool in diastolic dysfunction of grade ll and above.

Persistent Aortic Stiffness and Left Ventricular Hypertrophy in Children of Diabetic Mothers

BackgroundFetuses of diabetic mothers develop left ventricular (LV) hypertrophy and are at increased long-term risk of cardiovascular disease. In our previous longitudinal study from midgestation to late infancy we showed persistence of LV hypertrophy and increased aortic stiffness compared with infants of healthy mothers, the latter of which correlated with third trimester maternal hemoglobin A1c. In the present study, we reexamined the same cohort in early childhood to determine if these cardiovascular abnormalities persisted. MethodsHeight, weight, and right arm blood pressure were recorded. A full functional and structural echocardiogram was performed with offline analysis of LV posterior wall and interventricular septal diastolic thickness (IVSd), systolic and diastolic function, and aortic pulse wave velocity. Vascular reactivity was assessed using digital thermal monitoring. Participants also completed a physical activity questionnaire. ResultsTwenty-five children of diabetic mothers (CDMs) and 20 children from healthy pregnancies (mean age, 5.6 ± 1.7 and 5.3 ± 1.3 years, respectively; P = not significant) were assessed. Compared with controls, IVSd z score was increased in CDMs (1.2 ± 0.6 vs 0.5 ± 0.3, respectively; P = 0.006), with one-fifth having a z score of more than +2.0. Aortic pulse wave velocity was increased in CDMs (3.2 ± 0.6 m/s vs 2.2 ± 0.4 m/s; P = 0.001), and correlated with IVSd z score (R2 = 0.81; P = 0.001) and third trimester maternal A1c (R2 = 0.65; P < 0.0001). Body surface area, height, weight, blood pressure, vascular reactivity, and physical activity scores did not differ between groups. Our longitudinal analysis showed that individuals with greater IVSd, and aortic stiffness in utero, early and late infancy also tended to have greater measures in early childhood (P < 0.001 and P < 0.0001, respectively). ConclusionsCDMs show persistently increased interventricular septal thickness and aortic stiffness in early childhood.

Evaluation of echocardiographic variables of morphometry and function in horses submitted to minimally invasive partial pericardiotomy

ABSTRACT This study aimed to evaluate the impact of minimally invasive partial pericardiotomy on echocardiographic variables of morphometry and function in healthy horses. Minimally invasive pericardiotomy was performed in six healthy horses. Echocardiographic evaluation was executed in different moments: prior to the surgical procedure (M0); 24 hours post procedure (M1); 72 hours post procedure (M2) and 28 days post procedure (M3). The following variables were measured: Right ventricular internal diameter in diastole and systole (RVd and RVs), interventricular septum thickness in diastole and systole (IVSd and IVSs), left ventricular internal diameter in diastole and systole (LVd and LVs), left ventricular free wall thickness in diastole and systole (LVFWd and LVFWs), aortic root diameter (Ao) and left atrial diameter (LA). From this data, the following variables were calculated: fractional shortening (FS%), fractional thickening of the interventricular septum (IVS%), fractional thickening of the left ventricular free wall (LVFW%) and the relationship between left atrial and aortic diameters (LA/Ao). After 28 days, a new thoracoscopy was performed for inspection of the thoracic cavity. In M1 and M2 ECO evaluations, a statistically significant change in LVFW and a decrease in RVd, LVd, LVFWs, LA, LVs, FS% and IVS was documented. Pericardiotomy is a promising technique in horses, with minor postoperative complication. The variations in the echocardiographic parameters were transient and did not cause hemodynamic damage to the animals.

Echocardiographic predictors of cardiovascular morbidity and mortality in women from the general population.

Global longitudinal strain (GLS) is a strong predictor of adverse cardiovascular outcome in men. However, studies have indicated that GLS may not predict cardiovascular outcomes as effectively in women. The aim of this study was to identify echocardiographic predictors of cardiovascular morbidity and mortality in women from the general population. A total of 1245 women from the general population free of heart failure (HF) and atrial fibrillation had an echocardiographic examination performed including tissue Doppler imaging. In this subset, 747 women had images eligible for strain analysis. Endpoint was a composite of acute myocardial infarction, HF, and cardiovascular death. During follow-up (median 12.5 years), 162 women (13.0%) reached the composite outcome. These women had higher left ventricular (LV) mass index (LVMI), more LV hypertrophy, lower E/A, higher E/e', larger LV dimensions, and longer deceleration time. LVMI and e' remained as significant predictors of the composite outcome [LVMI: hazard ratio (HR) 1.10, 95% confidence interval (CI) 1.03-1.17, P = 0.004, per 5 g/m2 increase] (e': HR 1.53, 95% CI 1.07-2.20, P = 0.020, per 1 cm/s decrease) after adjusting for age, hypertension, systolic blood pressure, diabetes mellitus, total cholesterol, smoking status, prevalent ischaemic heart disease, LV ejection fraction, E/e', E, E/A, interventricular septum thickness in diastole, left ventricular posterior wall in diastole, a', body surface area, and pro-brain natriuretic peptide. GLS was not an independent predictor of outcome after multivariable adjustment. The degree of LV hypertrophy assessed as LVMI and diastolic dysfunction evaluated by e' are associated with adverse cardiovascular outcome in women from the general population.

Effect of a Weight Loss Program on Biochemical and Immunological Profile, Serum Leptin Levels, and Cardiovascular Parameters in Obese Dogs.

This study aimed to investigate the effects of a weight loss program (WLP) on biochemical and immunological profile, and cardiovascular parameters in a cohort of dogs with naturally occurring obesity. Eleven obese dogs [body condition scoring (BCS), ≥7/9] were enrolled into the study and underwent clinical and cardiovascular examination, and blood testing before (T0) and after 6 months (T1) of WLP. Eleven normal weight (BCS, 4/5) healthy dogs were used as a control (CTR) group. Compared to the CTR group, at T0 obese dogs expressed higher serum leptin concentrations (p < 0.0005) that significantly decreased after weight loss (p < 0.005) but remained higher than the CTR group. Furthermore, obese dogs showed considerably lower levels (p < 0.0005) of regulatory T cell (Treg) compared to the CTR group, but they did not change after weight loss at T1. In obese dogs, tumor necrosis factor (TNF)-α and interleukin (IL)-6 concentrations were substantially reduced at T1 (p < 0.0001 and p < 0.005). Regarding the cardiovascular parameters, only one obese dog was hypertensive at T0, and systolic blood pressure values showed no significant differences at the end of the WLP. The ratio of interventricular septal thickness in diastole to left ventricle internal diameter in diastole (IVSd/LVIDd) was significantly greater in obese dogs at T0 than in the CTR group (p < 0.005). It decreased after weight loss (p < 0.05). In obese dogs, troponin I level significantly reduced with weight loss (p < 0.05), while endothelin-1 level did not differ statistically. The results suggest that the immune dysregulation in the presence of high leptin levels and reduced number of Treg could affect obese dogs as well as humans. Based on our findings, we may speculate that a more complete immune-regulation restore could be obtained by a greater reduction in fat mass and a longer-term WLP. Finally, left ventricular remodeling may occur in some obese dogs. However, in canine species, further studies are needed to investigate the impact of obesity and related WLP on cardiovascular system.

Guanxinshutong capsule ameliorates cardiac function and architecture following myocardial injury by modulating ventricular remodeling in rats

Guanxinshutong capsule (GXST), which consists of five traditional Chinese medicines, has been used for a long time in China for the treatment of cardiovascular diseases, such as coronary artery disease and myocardial infarction. However, the effects on GXST on myocardial injury (MI) have not been studied in detail. In these experiments, we found that GXST administration decreased MI-associated ventricular remodeling (VR) with a reduction in interventricular septal thickness in diastole (IVSd), left ventricular posterior wall diameter in systole (LVPWs), and left ventricular posterior wall diameter in diastole (LVPWd) to ameliorate cardiac function and architecture, as measured by echocardiography. Furthermore, histological analysis showed that GXST could ameliorate pathological alterations in the myocardium. And Sirius red staining, wheat germ agglutinin staining and inflammation-related immunohistochemistry results showed that GXST ameliorated the fibrosis areas, cardiac hypertrophy and inflammation (IL-6 and TNF-α). In addition, GXST upregulated intercellular junction proteins (N-cad and Cx-43) and downregulated the angiogenesis-related proteins (PDGF and VEGFA), myocardial fibrosis-related proteins (TGF-β1), and matrix metalloproteinase (MMP-2 and MMP-9). We also found that GXST medium-dose group (1 g/kg/d) dosage was the most efficacious. In conclusion, GXST protected cardiac tissues against MI by reducing VR, thus indicating the potential application of GXST in the treatment of MI.

Global Longitudinal Strain, Ejection Fraction, Ventriculo‐Arterial Coupling and Their Interrelationships in Heart Failure Patients with Different Phenotypes

Ejection fraction (EF) is a popular metric to evaluate left ventricular (LV) systolic function. The EF is a ratio, based on paired volume measurements, similar as the more recently introduced ventriculo‐arterial coupling (VAC) index, being the ratio of two elastances. Their dimensionless nature requires consideration of the associated companion (i.e., the hypotenuse calculated from the constituent pair and denoted as EFC and VACC, respectively). This insight becomes clear when considering the LV volume domain representation.Global longitudinal strain (GLS) has been advanced as a preferred alternative for EF. Reportedly, the connection between EF and GLS is weak, thus confirming that these ratio‐based metrics focus on partial and likely dissimilar aspects of LV pump function. To overcome these limitations the present study addresses the relationships between GLS and EF or VAC (assuming vanishing intercept), as well as the newly introduced complementary metrics EFC and VACC.In 25 heart failure (HF) patients (43 – 83 years, 9 women) end‐systolic volume (ESV), end‐diastolic volume (EDV), diastolic interventricular septal thickness (IVST), and posterior wall thickness (PWT) were determined by echocardiography. Data are analyzed following informed consent. IVST and PWT were used to derive LV mass (LVM). GLS was obtained via speckle tracking echocardiography. When appropriate, these data were indexed (i) to body surface area (BSA).Significant sex‐specific differences were found for BSA (P&lt;0.0001), LVM (P=0.04) and stroke volume (P=0.02), but the latter not when normalized to BSA. The volume regulation graph (VRG) which relates ESV to EDV yields R=0.92, implying an inverse nonlinear relationship, either logarithmic or of the more robust type EF = 1+c1ESV / (c2+ESV), where c1 and c2 are population‐based constants. These data indicate that a sex‐specific cut‐off at ESVi=30 mL/m2 for men and at ESVi=20 mL/m2 for women separates the two major HF phenotypes, also demonstrating that the current practice of phenotyping via the ratio based metric EF is undesired and not required. LVM correlates (P&lt;0.001) with EDV (R=0.76) and with EFC (R=0.76). GLS moderately correlates with EF (R=−0.63, P&lt;0.001), VAC (R=−0.65, P&lt;0.001), EFC (R=0.49, P=0.025), and with VACC (R=0.43, P=0.03).The interpretation of EF, VAC and GLS in terms of physiology is debatable, as each refers to a ratio without physical dimension(s). In contrast, EFC and VACC carry a clear physical unit (namely mL), comparable to the primary variables ESV and EDV. The fact that GLS only moderately correlates with major clinically used metrics such as EF and VAC, suggests that there is a future place for the GLS companion, which deserves evaluation of its physiology‐based impact.Support or Funding InformationnoneEjection fraction (EF) versus end‐systolic volume index (ESVi) for two heart failure (HF) phenotypes, distinguished on the basis of a criterion applied to ESVi, which differs for women (red line) and men (blue line).Figure 1

Evaluation of left ventricular myocardial function in patients with aortic stenosis by layer-specific strain

Objective To investigate the value of layer-specific strain in evaluating the changes of left ventricular three layers and segmental myocardial function in patients with different degree of aortic stenosis (AS). Methods Ninety-eight AS patients were selected as AS group from December 2017 to June 2019 in Henan Provincial People′s Hospital, they were divided into mild AS group(30 cases), moderate AS group(33 cases), severe AS group(35 cases); 30 healthy subjects were enrolled as control group.Longitudinal strain (LS), circumferential strain (CS) of endocardium, mid-myocardium, epicardium, global full thickness and each segment of left ventricular myocardium were measured by layer-specific strain and then compared. Results Compared with the control group, Vmax, PPG, interventricular septal thickness in diastole(IVSD), left ventricular posterior wall thickness in diastole(LVPWD), left ventricular mass index(LVMI), and E/e increased in all three AS groups(all P 0.05). There were no significant difference in CS of endocardial, mid-myocardial, epicardial and global full-thickness myocardium layers in basal, middle and apical LV segments between mild AS group and control group(all P>0.05). CS of endocardial, mid-myocardial, epicardial and global full-thickness myocardium layers were decreased in moderate AS and severe AS groups compared with control group(all P<0.05). CS of endocardial, mid-myocardial myocardium layers in basal and middle LV segments were decreased in moderate AS group compared with control group(all P<0.05). CS of three myocardium layers in basal, middle and apical LV segments were decreased in severe AS group compared with control group(all P<0.05). Conclusions Layer-specific strain can quantitatively evaluate left ventricular three layers and segmental myocardial function in patients with aortic stenosis, and has certain clinical application value. Key words: Echocardiography; Layer-specific strain; Aortic stenosis; Ventricular function, left

Percutaneous Intramyocardial Septal Radiofrequency Ablation for Interventricular Septal Reduction: An Ovine Model with 1-Year Outcomes

Background: Percutaneous intramyocardial (PIM) septal radiofrequency ablation (SRA) is a novel treatment approach for hypertrophic obstructive cardiomyopathy patients, but there has been lack of a large animal model to study PIM-SRA. We aimed to validate the long-term safety and efficacy of PIM-SRA and to observe pathological changes of the ablated interventricular septum (IVS) in a healthy sheep model. Methods and Results: Twelve sheep were randomized to the PIM-SRA group (n = 6) and the sham group (n = 6). In the PIM-SRA group, a radiofrequency (RF) electrode was inserted into the IVS with a maximum power of 80 W for 5 min. In the sham group, the RF electrode tip was positioned in the IVS segment but without RF power delivery. Septal hypokinesis was seen in all PIM-SRA group animals immediately after the procedure; the systolic wall thickening rate and motion amplitude of the ablated region decreased (p < 0.01), and the diastolic IVS thickness also decreased significantly over time (p < 0.01). ECG showed that all the sheep had normal sinus rhythm during the follow-up. Pathological examinations revealed scar tissue in the ablated region as expected. Conclusions: PIM-SRA produced precisely ablated myocardial tissue, reduced the IVS thickness significantly, preserved the global LV function, and avoided the incidence of conduction system damage in the long term. PIM-SRA was found to be a safe and effective minimally invasive septal reduction therapy.

P2563Effects of rivaroxaban on cardiac remodeling after experimental myocardial infarction in mice

Abstract Background Rivaroxaban, a direct activated factor X (FXa) inhibitor, has been established for prevention and treatment of arterial and venous thrombosis. Although FXa plays an important role in thrombosis, FXa also involves in inflammation via the protease-activated receptor (PAR)-1 and PAR-2 pathway. We assessed the hypothesis that rivaroxaban might protect cardiac remodeling after myocardial infarction (MI) in mice. Methods MI was induced in wild-type mice by permanent ligation of the left anterior descending coronary artery. At 1 day after MI, mice were randomly assigned to the rivaroxaban and vehicle groups. In the rivaroxaban group, the mice were provided with regular chow diet including rivaroxaban (2400ppm) after the randomization. We evaluated the cardiac function by echocardiography, expression of mRNA and protein in the infarcted and non-infarcted area 7 days after MI. Furthermore, we measured infarct size, infiltration of inflammatory cells by pathological analysis 7 days after MI. Results The fractional shortening (%FS) and Interventricular Septal thickness in diastole (IVSTd) was significantly improved 7 days after MI in the rivaroxaban group compared with the vehicle group (%FS, p=0.01; IVSTd, p=0.013). As for pathological analysis, rivaroxaban decreased infarct size (p=0.026) and the number of infiltrated macrophages in the non-infarcted area (p=0.011) compared with vehicle. The mRNA expression in tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β in the infarcted area and atrial natriuretic peptide (ANP) in the non-infarcted area was significantly lower in the rivaroxaban group compared with the vehicle (TNF-α, p=0.015; TGF-β, p=0.019; ANP, p=0.012). PAR-1 and PAR-2 mRNA expression in the infarcted area significantly decreased 7 days after MI in the rivaroxaban group compared with the vehicle (PAR-1, p=0.005; PAR-2, p=0.037). Furthermore, western blot analysis demonstrated that the phosphorylation of Extracellular Signal-regulated Kinase (ERK) and c-Jun N-terminal Kinase (JNK) in the non-infarcted area significantly decreased 7 days after MI in the rivaroxaban group compared with the vehicle (ERK, p=0.015; JNK, p=0.002). Conclusions The present study showed that rivaroxaban protected against cardiac dysfunction, probably due to the suppression of PAR-mediated increase of pro-inflammatory cytokines post-MI. Rivaroxaban might be potentially effective for improving the cardiac remodeling after MI. Acknowledgement/Funding This study was supported in part by trust-research grant from Bayer Yakuhin, Ltd.

P3434Galectin-3 identifies healthy subjects at risk of developing (pre-)diastolic dysfunction

Abstract Background/Introduction Biomarkers might be useful to identify healthy subjects who are at risk of developing diastolic dysfunction. Cardiac remodeling, in particular fibrosis, is a hallmark of diastolic dysfunction. Previous (pre)clinical studies have linked galectin-3 to fibrogenesis. Therefore, we aimed to evaluate whether galectin-3 would be able to identify apparently healthy individuals who are at risk of developing pre-clinical diastolic dysfunction. Purpose To study whether galectin-3 is able to identify healthy subjects who are at risk of developing pre-clinical diastolic dysfunction over time. Methods We measured both galectin-3 and B-type natriuretic peptide (BNP) in 1.500 participants of the population study LifeLines. Based upon the biomarker profile, we selected 88 subjects with elevated galectin-3 (&gt;14.3 ng/mL; n=42) and with low galectin-3 (&lt;9.8 ng/mL; n=46) values, while all participants demonstrated low BNP. We matched these groups so other confounding variables like age, sex, kidney function (creatinine), body weight (BMI) and blood pressure were comparable between both groups. After approximately five years follow up, we invited those 88 participants to determine the level of diastolic dysfunction using echocardiography. Statistical analyses were performed in IBM SPSS Statistics 25 and StataMP 13. Results We included 88 participants at a median age of 50 years (standard deviation ± 11 years) in this case-control study. Besides the galectin-3 levels, all other variables were adequately matched and fully comparable between both groups. Obviously, galectin-3 levels (median, IQR) were markedly different between the groups (galectin-3 levels 7.35 ng/L (6.9 - 8.6) vs 16.4 ng/L (15.1- 17.8), P&lt;0.001). Subjects with elevated galectin-3 demonstrated signs of structural cardiac remodeling: enlarged left atrial diameter (35.3 mm vs. 37.3 mm P=0.034), and larger diastolic interventricular septum thickness (IVS) (9.4 mm vs. 10.1 mm P=0.038), and a smaller left ventricular end-diastolic internal dimension index (LVIDd Index) (2.3 cm/m2 vs. 2.2 cm/m2 P=0.026), a smaller left ventricular end diastolic volume (LVEDV) (98.9 mL vs. 89.9 mL P=0.025). In addition, they exhibited several indicators of worse diastolic function, such as a higher E/e' ratio (5.2 vs. 5.9, P=0.046), while there was no significant difference in the left ventricular ejection fraction (60.8% vs. 59.9%, P=0.110). Conclusion Elevated galectin-3, when fully matched for confounding factors, is associated with the development of preclinical-diastolic dysfunction before onset of clinical symptoms. Our data suggest that substantial elevations of galectin-3 in apparently healthy subjects hint towards preclinical cardiac dysfunction. Acknowledgement/Funding Dutch Heart Foundation 2015T034; NWO VIDI, grant 917.13.350; ERC CoG 818715, SECRETE-HF